Abstract
Membranes are of outmost importance to allow for specific signal transduction due to their ability to localize, amplify, and direct signals. However, due to the double-edged nature of reactive oxygen species (ROS)—toxic at high concentrations but essential signal molecules—subcellular localization of ROS-producing systems to the plasma membrane has been traditionally regarded as a protective strategy to defend cells from unwanted side-effects. Nevertheless, specialized regions, such as lipid rafts and caveolae, house and regulate the activated/inhibited states of important ROS-producing systems and concentrate redox targets, demonstrating that plasma membrane functions may go beyond acting as a securing lipid barrier. This is nicely evinced by nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases (NOX), enzymes whose primary function is to generate ROS and which have been shown to reside in specific lipid compartments. In addition, membrane-inserted bidirectional H2O2-transporters modulate their conductance precisely during the passage of the molecules through the lipid bilayer, ensuring time-scaled delivery of the signal. This review aims to summarize current evidence supporting the role of the plasma membrane as an organizing center that serves as a platform for redox signal transmission, particularly NOX-driven, providing specificity at the same time that limits undesirable oxidative damage in case of malfunction. As an example of malfunction, we explore several pathological situations in which an inflammatory component is present, such as inflammatory bowel disease and neurodegenerative disorders, to illustrate how dysregulation of plasma-membrane-localized redox signaling impacts normal cell physiology.
Highlights
When looking to the world surrounding us, it becomes pretty clear that animals and plants are adapted to the particular conditions of the habitats in which they live
It is becoming clear that the basis for redox signaling specificity starts with compartmentalization of producers and targets, the study of the localization of redox systems at particular plasma membrane regions has not gained much attention until recently
Notwithstanding, membrane architecture and organization of reactive oxygen species (ROS)-generating enzymes in distinct lipid domains has the potential to explain how efficient redox signal transmission could be achieved, while risk of damage intrinsically associated to ROS is minimized
Summary
When looking to the world surrounding us, it becomes pretty clear that animals and plants are adapted to the particular conditions of the habitats in which they live. The product of a spontaneous or SOD-catalyzed O2 − conversion is hydrogen peroxide (H2 O2 ) [24] The role of this oxidant in signal transduction is nowadays widely accepted, since its chemistry fully adapts to the characteristics that qualify a molecule as a second messenger. H2 O2 can be produced by several enzymatic systems, mostly through univalent reduction of O2 − and directly [11], and is degraded by devoted protein scavengers (catalase, peroxiredoxins, glutathione peroxidases) [25] Additional strategies, such as compartmentalization of H2 O2 production and regulated distribution using dedicated membrane channels, are employed to preserve homeostatic control of its levels [26]. It has been hypothesized that OH -mediated crosslinking is the basis of the supramolecular organization of cell structures, such as the plasma membrane [32]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
